Abstract
BACKGROUND: Mycobacterium abscessus subsp. abscessus (M. abscessus) is a rapidly growing mycobacterium that is resistant to most antibiotics. The number of patients with pulmonary disease caused by M. abscessus is increasing in several regions, and therapy involves long-term antibiotic combination treatments, although no standard treatment regimen has been established. OBJECTIVES: To examine candidate regimens for maintenance of antimicrobial treatment against M. abscessus by measuring MIC using the three-drug chequerboard method. METHODS: We evaluated the drug susceptibility of 70 clinical isolates of M. abscessus using the three-drug chequerboard method. We tested the antimycobacterial agents bedaquiline, clofazimine, amikacin, and sitafloxacin (which showed a relatively low MIC range when used as single agents) alone and in combinations. RESULTS: The three-drug combinations of bedaquiline/clofazimine/amikacin, and bedaquiline/clofazimine/sitafloxacin were studied. Among isolates for which the fractional inhibitory concentration index (FICI) could be calculated, 29/70 isolates (41%) and 11/70 isolates (16%) showed a synergistic response (FICI ≤0.75) with combined use of bedaquiline/clofazimine/amikacin, or with bedaquiline/clofazimine/sitafloxacin, respectively. CONCLUSIONS: The combination of bedaquiline with clofazimine plus either amikacin or sitafloxacin may be useful as maintenance regimens when treating pulmonary disease caused by M. abscessus.